Disturbance of arterial blood circulation is one of the most common diseases in industrial countries. Mostly, the cause of this disease is arteriosclerosis, which leads to a constriction or even occlusion of the artery. Modern medicine treats highly localised occlusions by catheter expansion (percutaneous transluminal angioplasty) and possibly placement of a stent. Lengthier occlusions, predominantly at the leg and at the heart, are by-passed by a natural or artificial vessel (bypass-surgery). The ideal vessel-replacement material for arteries having small calibers (about 4 to 6 mm) is the particularly suitable v. saphena magna (skin deep long main vein at the leg). This vein often is not available because of preceding varicosity surgery or it is not suitable to be implanted for other reasons. In case the patient's own vein cannot be used, the implantation of an artificial vessel (prothesis) becomes necessary.
The present inventor has a professional interest in the success of surgical procedures in which, if no bodily vein is available, a tubular implant such as a graft, graft-stent or stent is placed in a part of the (cardio-) vascular system of a patient. A complicating factor of this kind of surgical procedures is that the range of materials for the implants is relatively small and, within this range, materials are prone to occlusion due to adhered, coagulated blood (thrombosis). As soon as blood has adhered to the wall of a tubular implant and is coagulated, there will be no possibility for removal of the coagulated blood, the lumen likely to be occluded after a certain period of time. The risk of thrombosis is particularly high for artificial blood vessels with relatively small diameters (up to about 7 mm). Since thrombosis is life-threatening, occlusion of the artificial blood vessels must be avoided, which is up to now managed by the use of drugs (anticoagulants).
Grafts are usually longer than stents, and, therefore, in general the danger of occlusions is significantly higher for grafts. Grafts may have a length between about 20 mm and about 800 mm, the diameters of the grafts depending on the intended application and being within a range of about 2 mm to about 30 mm. Smaller graft diameters are for instance needed for bypasses to the foot artery or the knee-joint artery, whereas larger diameters are needed for aortocoronary bypasses. Grafts with diameters less than about 2 mm have not yet been artificially realized.
The thrombogenic effect of artificial blood vessels is known in the state of the art. There are a large number of disclosures, which discuss the surface topography of the luminal walls of bodily prostheses. These documents teach to increase the blood flow velocity while eliminating or reducing any kind of turbulent flow, see for instance U.S. Pat. No. 5,108,417 or WO 00/38591.
The creation of (quasi-) turbulent flow is suggested in WO 01/04532, a disclosure relating to industrial conduits and conduit elements. This disclosure contains no hint or suggestion to apply its teaching to medicine and to surfaces having contact with blood, such as bodily implants. The document is in relation to a surface topography on the inner wall of a conduit that will generate a turbulent or quasi-turbulent boundary layer between the inner wall of the conduit and the main flow of the medium. This specific topography is said to enhance the capacity of the conduit to entrain in the fluid flow particles which are disposed on the wall of the conduit.
Trying to find a way to reduce the thrombogenity of artificial blood vessels, the present inventor has noticed that natural surfaces in lumens of the human body are seldom completely smooth. Yet, the flow of fluid through these lumens is laminar, rather than turbulent, more or less everywhere in the body (the chambers of the heart are an obvious exception), because in general turbulent flow will irritate the inner walls of vessels.
Subsequent to these findings, the present inventor has conducted extensive investigations and experimentation with a view to discovering whether one can learn from the natural topography of lumens in the body so as in some way to inhibit adherence of particles from blood, and, in consequence, render thrombosis less likely.
In particular, experimentation with streamline visualization and cine filming, in channels with various patterns of wall surface topography, has revealed a possible mechanism and explanation that offers exciting possibilities to inhibit adherence of particles from blood on inner walls of medical devices.
The mechanism is based on the classic distribution of flow velocity across the transverse cross section of a lumen such as a tube in which laminar flow is occurring which is known in the field of fluid dynamics. This classic distribution shows a parabolic flow profile having a maximum velocity along the central axis of the lumen, and a velocity which steadily falls, as one moves from the center of the lumen to the wall of the lumen, with the fluid which is in contact with the wall of the lumen having a zero velocity (see FIG. 1 below in which the vertical axis denotes flow velocity and the horizontal axis denotes the inside diameter d of a tube with a lumen of radius r and a circular cross-section centered on a long axis 0). It is believed that laminar flow occurs in various vessels and such laminar flow can be inferentially determined based on a dimensionless Reynolds number “Re” where Re=average velocity times the vessel inside diameter times the density of blood divided by the viscosity of blood. The Reynolds number of blood flow varies depending on the types of vessel and the location of the vessel within a mammalian body. For example, a study entitled “Two alternative Models Concerning the Perioaveoloar Microcirculation in Mammalian Lungs” by BRUNO GÜNTHERa, ENRIQUE MORGADOb, c* and MANUELA COCI{grave over (N)}A (available at http://www.scielo.cl/scielo.php?pid=S0716-97602005000100007&script=sci_arttext&tlng=en) indicates that Reynolds number Re for laminar vs. turbulent flow in the case of microcirculation, is about 0.03 in the arterioles, and about 0.0025 in the systemic capillaries, in contrast with the blood flow in the aorta, where Re=2349. In another study, “Coronary Flow Velocity and Disturbed Flow Predict Adverse Clinical Outcome After Coronary Angioplasty” by Kinlay et al., (available online at http://atvb.ahajournals.org/cgi/content/full/22/8/1334#R14-112431 or from Scott Kinlay, MBBS, PhD, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, Mass. 02115, the flow of a liquid is laminar if the Reynolds number is <2000.
Related to blood this means a long retention period of the blood cells tending to adhesion at the luminal wall. Natural blood vessels exhibit an anti-thrombogenic surface and thereby prevent the adhesion of the blood cells that precipitates a complex cascade of events, which leads to coagulation of the blood (thrombosis) and occlusion of the vessel. Up to now, all materials known for manufacturing of artificial blood vessels have no anti-thrombogenic surface and, especially with small calibers (smaller than 7 mm), tend to promote deposition of blood cells with consequential coagulation and thereafter occlusion due to the coagulated blood. Thus, posits the inventor, there exists a direct correlation between the likelihood of thrombosis and the flow velocity in the marginal zone of an artificial blood vessel or artificial surfaces, which are in constant contact with blood, in general.
Accordingly, the inventor advocates a medical device which reduces the thrombogenic effect by increasing the flow velocity in the marginal zone of a lumen of a medical device thereby to reduce the retention time of blood cells prone to adhesion in the marginal zone and thereby rendering the possibility of a thrombosis less likely.